ArticleTuberculosis (Edinburgh, Scotland)2019
Comparative pharmacokinetics of spectinamide 1599 after subcutaneous and intrapulmonary aerosol administration in mice.
Article in Tuberculosis (Edinburgh, Scotland), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Development and Evaluation of Aloperine-Loaded Nanostructured Lipid Carriers for the Treatment of Pulmonary Arterial Hypertension.International journal of nanomedicine · 2025Article
- Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Enhancing the therapeutic window for Spectinamide anti-tuberculosis Agents: Synthesis, Evaluation, and activation of phosphate prodrug 3408.Bioorganic & medicinal chemistry letters · 2024Article
- A modified BPaL regimen for tuberculosis treatment replaces linezolid with inhaled spectinamides.eLife · 2024Article
- Development of a Minimalistic Physiologically Based Pharmacokinetic (mPBPK) Model for the Preclinical Development of Spectinamide Antibiotics.Pharmaceutics · 2023Article
- Characterization of spectinamide 1599 efficacy against different mycobacterial phenotypes.Tuberculosis (Edinburgh, Scotland) · 2023Article
- Developing synergistic drug combinations to restore antibiotic sensitivity in drug-resistantAntimicrobial agents and chemotherapy · 2023Article
- Model-Based Exposure-Response Assessment for Spectinamide 1810 in a Mouse Model of Tuberculosis.Antimicrobial agents and chemotherapy · 2021Article
- Preclinical Evaluation of Inhalational Spectinamide-1599 Therapy against Tuberculosis.ACS infectious diseases · 2021Article
- Development and Characterization of a Dry Powder Formulation for Anti-Tuberculosis Drug Spectinamide 1599.Pharmaceutical research · 2019Article
- Sterilization of Mycobacterium tuberculosis infected samples using methanol preserves anti-tuberculosis drugs for subsequent pharmacological testing studies.Tuberculosis (Edinburgh, Scotland) · 2019Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Spectinamides are a novel series of spectinomycin analogs being developed for the treatment of tuberculosis. Intrapulmonary aerosol (IPA) administration of lead spectinamide 1599 has previously been shown to be more efficacious than subcutaneous (SC) administration at comparable doses. The objective of the current study was to characterize the disposition of 1599 in plasma and lungs in mice in order to provide a potential rationale for the observed efficacy differences. 200 mg/kg of 1599 was administered to healthy BALB/c mice by SC injection or by IPA delivery. Plasma and major organs were collected at specified time points until 8 h after dosing. Drug concentrations were measured by LC-MS/MS and analyzed by noncompartmental pharmacokinetic analysis. 1599 demonstrated rapid absorption into plasma after IPA and SC administration, resulting in very similar plasma exposure for both routes. In contrast, drug exposure in the lungs was 48 times higher following IPA as compared to SC administration, which is highly desirable as the lungs are the main site of infection in pulmonary TB. The higher local exposure in the lungs is likely the basis for the increased efficacy after IPA compared to SC administration. Overall, this study supports the pulmonary route as a potential pathway for the treatment of tuberculosis with 1599.
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